Journal ArticleDOI
Siponimod in the treatment of multiple sclerosis.
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TLDR
The results of a phase-III study suggest that siponimod may be beneficial in secondary progressive MS, at least in patients with disease activity.Abstract:
Introduction: Multiple sclerosis (MS) causes focal lesions of immune-mediated demyelinating events followed by slow progressive accumulation of disability. Over the past 2 decades, multiple medications have been studied and approved for use in MS. Most of these agents work by modulating or suppressing the peripheral immune system. Siponimod is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator that internalizes S1P1 receptors, thereby inhibiting efflux of lymphocytes from lymph nodes and thymus. There are promising data suggesting that it may also have a direct neuroprotective property independent of peripheral lymphocytopenia.Areas covered: We reviewed the pharmacology and the clinical and radiological effects of siponimod.Expert opinion: The selective effect of siponimod on the S1P1 and S1P5 receptors offers a favorable side-effect profile and transient bradycardia can be avoided by dose titration. A phase-II study showed that siponomod has dose-dependent beneficial effects in patients with relapsing remitting disease. The results of a phase-III study suggest that siponimod may be beneficial in secondary progressive MS, at least in patients with disease activity.read more
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References
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Journal ArticleDOI
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Mehrdad Matloubian,Charles G. Lo,Guy Cinamon,Matthew J. Lesneski,Ying Xu,Volker Brinkmann,Maria L. Allende,Richard L. Proia,Jason G. Cyster +8 more
TL;DR: It is established that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.
Journal ArticleDOI
A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis
Ludwig Kappos,Ernst Wilhelm Radue,Paul O'Connor,Chris H. Polman,Reinhard Hohlfeld,Peter A. Calabresi,Krzysztof Selmaj,Catherine Agoropoulou,Malgorzata Leyk,Lixin Zhang-Auberson,Pascale Burtin +10 more
TL;DR: Both doses of oral fingolimod improved the relapse rate, the risk of disability progression, and end points on MRI and were superior to placebo with regard to MRI-related measures.
Journal ArticleDOI
Defining the clinical course of multiple sclerosis: The 2013 revisions
Fred D. Lublin,Stephen C. Reingold,Jeffrey A. Cohen,Gary Cutter,Per Soelberg Sørensen,Alan J. Thompson,Jerry S. Wolinsky,Laura J. Balcer,Brenda Banwell,Frederik Barkhof,Bruce F. Bebo,Peter A. Calabresi,Michel Clanet,Giancarlo Comi,Robert J. Fox,Mark S. Freedman,Andrew D. Goodman,Matilde Inglese,Ludwig Kappos,Bernd C. Kieseier,John A. Lincoln,Catherine Lubetzki,Aaron E. Miller,Xavier Montalban,Paul O'Connor,John Petkau,Carlo Pozzilli,Richard A. Rudick,Maria Pia Sormani,Olaf Stüve,Emmanuelle Waubant,Chris H. Polman +31 more
TL;DR: Refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression are proposed and strategies for future research to better define phenotypes are outlined.
Journal ArticleDOI
Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.
Jeffrey A. Cohen,Frederik Barkhof,Giancarlo Comi,Hans Peter Hartung,Bhupendra Khatri,Xavier Montalban,Jean Pelletier,Ruggero Capra,Paolo Gallo,Guillermo Izquierdo,Klaus Tiel-Wilck,Ana de Vera,James Jin,Tracy Stites,Stacy Wu,Shreeram Aradhye,Ludwig Kappos +16 more
TL;DR: This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a.
Journal ArticleDOI
Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists.
Suzanne M. Mandala,Richard Hajdu,James D. Bergstrom,Elizabeth J. Quackenbush,Jenny Xie,James A. Milligan,Rosemary A. Thornton,Gan-Ju Shei,Deborah Card,CarolAnn Keohane,Mark Rosenbach,Jeffrey J. Hale,Christopher L. Lynch,Kathleen M. Rupprecht,William H. Parsons,Hugh Rosen +15 more
TL;DR: It is shown that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolites of the immunosuppressive agent FTY720.
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